Critics Say Upjohn Hid Data On Drug

January 20, 1992|by GINA KOLATA, The New York Times

For two decades, the drug company that makes Halcion, the world's best-selling sleeping pill, concealed data from the Food and Drug Administration showing that it caused significant numbers of serious psychiatric side effects, critics contend.

The critics, who include drug and psychiatric experts who have analyzed company records produced in a recent court case, say the data show the pill was more dangerous than other sleeping pills and was more likely to cause symptoms like amnesia, paranoia, depression, and hallucinations. The assertions have prompted the Food and Drug Administration to begin an investigation of the manufacturer, the Upjohn Co., and persuaded Great Britain to ban the drug outright in October.

Upjohn denies that any data were concealed, and insists that Halcion is just as safe as other drugs of its class. "We can find no evidence of any intentional wrongdoing," said Dr. Theodore Cooper, chairman and chief executive officer of Upjohn, which is based in Kalamazoo, Mich. "We've got millions of patients out there. We would not knowingly put out anything that was not safe and effective."

Cooper said Halcion had no more side effects than other sleeping pills of its class, and that although a few recording errors had been found in the company's data, these made no difference in the overall assessment of Halcion.

Halcion has been sold in the United States since 1983 and is marketed in 89 other countries. The pill, which Upjohn has advertised as differing from its competitors by promoting nighttime sleep without daytime drowsiness, represents 8 percent of the company's sales, which were $2.5 billion in the first nine months of 1991.

Critics assert that Upjohn has failed to report all the side effects it observed with Halcion, or concealed adverse findings in various subtle ways. They say, for example, that Upjohn dropped subjects from its clinical studies who had bad reactions to Halcion, or balanced such patients by incorrectly reporting the same side effects among subjects in the study's control group, who received different sleeping pills for comparison.

The unpublished data from the Halcion studies were revealed recently as a result of a lawsuit filed by Ilo Grundberg, a 57-year-old woman living in Hurricane, Utah, who killed her mother at midnight of the day before the mother's 83rd birthday, shooting her eight times. She then placed a birthday card in her mother's hand. Grundberg contended that Halcion had made her psychotic, and charges against her were ultimately dismissed.

Upjohn settled the Grundberg lawsuit for an unspecified amount just before it was to go to trial last August. The company had been obliged to provide much new data about Halcion to the plaintiff's lawyers, and obtained a court order to keep the data secret. But the court order did not prevent the data from reaching drug regulatory authorities, and as a result the FDA has begun an investigation of the company, while the agency's counterpart in Britain decided to ban Halcion altogether. The British authorities told Upjohn in a letter that it was highly unlikely they would have approved the drug had they known about the data earlier.

Upjohn officials said they were astonished by Britain's decision and were appealing it.

The leading critic of Halcion is Dr. Ian Oswald, a Scottish psychiatrist who was called as an expert witness by Grundberg's lawyers. Oswald, now retired, was head of the department of psychiatry at the University of Edinburgh and spent 30 years doing research on sleep, including a study of Halcion. Oswald said he expected to spend three hours on the witness stand. But after examining internal company records and memorandums, he and his wife, Dr. Kirstine Adam, then spent two years combing through Upjohn's data.

Oswald said he has concluded that "the whole thing has been one long fraud." He asserted that Upjohn has known about the extent of the drug's adverse effects for 20 years and "concealed these truths from the world." It was largely on the basis of his analysis presented to the British drug regulatory agency that Britain banned the drug.

Another critic of Halcion is Dr. Graham Dukes, a former medical director of the Dutch drug regulatory agency who is now professor of drug policy studies at the University of Gronigen in Denmark. Dukes, who saw some of the company's internal data, said that Upjohn's data were presented so as to minimize Halcion's adverse effects.

"It is inconceivable that this could have happened accidentally," he said. "The events in the clinical trials were so clear in the original patient records and so numerous that they could not have been overlooked. There must have been an intent somewhere."